2.1. TERMINOLOGY
For the purposes of this invention the terminology and basic concepts used are defined as described below.
Skin fibroblasts (SF) are derived from connective tissue of the skin. Adipose cells (also referred to as adipocytes or fat cells) are cells with little cytoplasmic volume that possess large vacuoles containing triglycerides and are usually derived from adipose tissue.
The term "cell genotype" describes the genetic constitution of a cell.
The term "cell phenotype" or "phenotypic expression" describes the appearance or other characteristics of a cell resulting from the interaction between its genetic constitution and the environment.
The term "transformation/neodifferentiation" or "transformed/neodifferentiated cell" is used to connote the occurrence of a change from a fully differentiated normal cell type to a new cell phenotype; this may occur in vivo or in vitro. This change may be complete, i.e., the conversion of a fully differentiated cell type into a newly differentiated fully mature cell type, or it may be partial, i.e., representing various stages along the transformation/neodifferentiated process. The occurrence of abnormal phenotypic expressions during such a transition can be monitored in vitro.
The term "cancer predisposition" is used to describe the transformed/neodifferentiated phenotype when a discussion about in vivo susceptibility mechanisms is indicated. Predisposition to cancer suggests the higher than average occurrence of cancer in certain population groups. Cancer predisposition appears to be due to the interaction of genetic and environmental factors. In some instances, however, cancer predisposition can be described as primarily constitutive (genetic), while in others it is apparently principally environmentally induced.
The terms "neoplasia" and "tumor" will be qualified, where necessary, as benign or maglignant. All other synonyms for cancer are used to mean a tumor which is malignant by the usual criteria in vivo, i.e., a tissue which grows progessively and which, if left untreated, will kill the host organism.
The term "autosomal dominant cancer trait" is used to describe susceptibility alleles perceived through a statistical analysis of various genetic models. For example, in a pattern of inheritance involving autosomal dominant genes in which one parent is heterozygous (T/t) for an autosomal dominant gene (T) and the other parent is homozygous for the normal allele (t/t), each child (T/t .times.t/t) has a 50 percent chance of receiving the abnormal allele T, thus being affected, and a 50 percent chance of receiving the normal allele t, thus being normal. Hence, on the average, half of the children will have the trait. (For a more complete discussion of this topic see Thompson and Thompson, in Genetics in Medicine, 1973, W. B. Saunders Company, Philadelphia, pp. 48-88).